title: Mitochondrial D310 D-Loop instability and histological subtypes in radiation-induced cutaneous basal cell carcinomas.
abstract: BACKGROUND
  Basal cell carcinoma (BCC) is the most frequent skin cancer. An elevated prevalence of BCC has been associated with radiation, namely after the Tinea capitis epilation treatment, being these tumors described as more aggressive. Mitochondrial DNA (mtDNA) mutations have been reported in many human tumors, but their occurrence in BCC is poorly documented.
  
  
  OBJECTIVE
  The purpose of this work was to evaluate BCC histological subtypes in individuals subjected to X-ray epilation for Tinea capitis treatment when compared to non-irradiated patients. Moreover we also wanted to evaluate mitochondrial D-Loop instability in both groups of BCCs in order to compare the frequency of D-Loop mutations in post-irradiation BCC versus sporadic BCC.
  
  
  METHODS
  228 histological specimens corresponding to BCCs from 75 irradiated patients and 60 non-irradiated patients were re-evaluated for histological subtype. Subsequently, we sequenced the D-Loop 310 repeat in blood, oral mucosa, tumor lesions and, whenever available, non-tumoral adjacent tissue from these patients.
  
  
  RESULTS
  The infiltrative subtype of BCC, considered to be more aggressive, was significantly more frequent in irradiated patients. BCC D-Loop D310 mutation rate was significantly higher in irradiated BCCs than in the non-irradiated ones. Moreover, it was associated with a higher irradiation dose. The presence of mtDNA heteroplasmy in patients' blood was associated with a higher mutation rate in the BCCs suggesting that a more unstable genotype could predispose to mtDNA somatic mutation.
  
  
  CONCLUSIONS
  Our results suggest that radiation-induced BCCs may be considered to be more aggressive tumors. Further studies are needed to clarify the role of mtDNA D-Loop mutations in tumors from irradiated patients.
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: mboaventura@ipatimup.pt.
authors.forename: Paula
authors.initials: P
authors.lastname: Boaventura
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: dina_pereira86@hotmail.com.
authors.forename: Dina
authors.initials: D
authors.lastname: Pereira
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: mmendes@ipatimup.pt.
authors.forename: Adélia
authors.initials: A
authors.lastname: Mendes
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: rbatista@ipatimup.pt.
authors.forename: Rui
authors.initials: R
authors.lastname: Batista
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: asilva@ipatimup.pt.
authors.forename: André Ferreira
authors.initials: AF
authors.lastname: da Silva
authors.affiliation: Hospital Pedro Hispano, Rua Dr. Eduardo Torres, 4464-513 Senhora da Hora, Portugal. Electronic address: Isabel.Guimaraes@ulsm.min-saude.pt.
authors.forename: Isabel
authors.initials: I
authors.lastname: Guimarães
authors.affiliation: Hospital Pedro Hispano, Rua Dr. Eduardo Torres, 4464-513 Senhora da Hora, Portugal. Electronic address: Mrinalini.Honavar@ulsm.min-saude.pt.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Honavar
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: jose@teixeiragomes.pt.
authors.forename: José
authors.initials: J
authors.lastname: Teixeira-Gomes
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal; Medical Faculty, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: jmlopes@ipatimup.pt.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lopes
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal; Medical Faculty, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: vmaximo@ipatimup.pt.
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal; Medical Faculty, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: psoares@ipatimup.pt.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006204:Hair Removal / Q000009:adverse effects*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D009690:Nucleic Acid Conformation; D010641:Phenotype; D012042:Registries; D012307:Risk Factors; D012535:Scalp / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014006:Tinea Capitis / Q000382:microbiology / Q000532:radiotherapy*
chemical_list: D004272:DNA, Mitochondrial
keywords: BCC; Basal cell carcinoma; D-Loop; Histological subtype; Radiation; Tinea capitis; basal cell carcinoma; mitochondrial; mt